Global Assessment Of Disease Activity Research Articles

Associations between Patient Global Assessment scores and pain, physical function, and fatigue in rheumatoid arthritis: a post hoc analysis of data from phase 3 trials of tofacitinib

BackgroundTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We examined the degree to which Patient Global Assessment of Disease Activity (PtGA) was driven by patient-reported assessments of pain (Pain), physical function, and fatigue in patients receiving tofacitinib 5 mg twice daily or placebo, each with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).MethodsThis post hoc analysis used data pooled from three randomized controlled trials in csDMARD-inadequate responder (csDMARD-IR) patients (ORAL Scan: NCT00847613; ORAL Standard: NCT00853385; ORAL Sync: NCT00856544). Using subgroup analysis from 2 × 2 tables, associations between PtGA and Pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at month 3 were evaluated using Pearson’s Phi correlation coefficients. To support the main analysis, associations between select patient-reported outcomes (PROs) were also evaluated in csDMARD-naïve (ORAL Start; NCT01039688) and biologic (b)DMARD-IR (ORAL Step; NCT00960440) patients.ResultsAcross csDMARD-IR treatment groups, low disease activity (defined as PtGA ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in PtGA were associated with mild Pain (Visual Analog Scale score ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in Pain; lack of Pain improvement was associated with little/no improvement in PtGA. In contrast, large proportions of csDMARD-IR patients who reported PtGA improvements did not report HAQ-DI or FACIT-F scores ≥ normative values (≤ 0.25 and ≥ 43.5, respectively) or changes in HAQ-DI or FACIT-F scores ≥ minimum clinically important difference (≥ 0.22 and ≥ 4.0, respectively). Generally, PtGA and Pain outcomes were moderately-to-strongly correlated at month 3 in csDMARD-IR patients, with weaker correlations evident between PtGA and HAQ-DI/FACIT-F outcomes. Similar findings were generally evident in csDMARD-naïve and bDMARD-IR patients.ConclusionsThis analysis supports the role of Pain as a key driver of PtGA in RA; physical function and fatigue play lesser roles in patients’ perceptions of disease activity. These findings corroborate the importance of improved PROs and attainment of low symptom states for optimizing patient care.Trial registrationClinicaltrials.gov: NCT00847613 (registered: February 19, 2009); NCT00853385 (registered: March 2, 2009); NCT00856544 (registered: March 5, 2009); NCT01039688 (registered: December 25, 2009); NCT00960440 (registered: August 17, 2009)

Lipid Profiles in Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis: A Cross-sectional Analysis

Objective. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease (AID) characterised by necrotising intravascular inflammation. Growing evidence suggests that immune system triggers altered lipid metabolism in AIDs. We investigated whether changes in lipid profile correlate with severity of disease in AAV. Methods. Seven lipid profiles were evaluated utilizing frozen serum samples from 67 patients registered in the Severance Hospital ANCA-associated VasculitidEs cohort by a chemistry autoanalyzer. The Birmingham Vasculitis Activity Score (BVAS) version 3 was used to measure patient’s assessment of global disease activity. The relationship between the BVAS with continuous variables was calculated by Pearson’s correlation analysis. Results. Thirty-five (52.2%), 19 (28.4%), and 13 (19.4%) patients were diagnosed with microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis, respectively. Patients’ mean age was 60.0 years, and 22 (32.8%) were male. Among the lipid profiles investigated, total cholesterol, high-density lipoprotein, and low-density lipoprotein, and apolipoprotein A1 and B were significantly associated with BVAS; apolipoprotein A1 showed the highest correlation with BVAS (r=-0.521, p＜0.001), remaining consistent even in patients with new-onset disease (r=-0.430, p=0.012). Apolipoprotein A1 had the highest association with the renal manifestation score among the clinical scores comprising BVAS (r=-0.457, p＜0.001). Conclusion. Decreased lipid levels, especially apolipoprotein A1, are relevant to increased AAV disease activity, and differ according to organ involvement. Measuring lipid profiles could have clinical implications regarding the assessment of global disease activity and organ involvement patterns. (J Rheum Dis 2020;27:261 -269)

Effect of Multidomain Disease Presentations on Patients With Psoriatic Arthritis in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry

To compare disease characteristics, quality of life (QOL), and work productivity of patients with psoriatic arthritis (PsA) who had multidomain vs single-domain presentations. Adults with PsA enrolled in the Corrona PsA/Spondyloarthritis Registry (March 2013-August 2018) were included. Six PsA disease domains were evaluated: enthesitis, dactylitis, peripheral arthritis (PA), nail psoriasis, axial disease, and skin disease. Patients were classified as having multidomain (≥ 2 domains) or single-domain disease presentations; biologic initiators were characterized separately. Linear regression models evaluated the association of multidomain presentations with disease characteristics, QOL, and work productivity vs single-domain presentations. Of 2617 patients with PsA, 1698 (64.9%) had multidomain presentations, 617 (23.6%) had single-domain presentations, and 302 (11.5%) had no active disease features. Of 354 biologic initiators, 289 (81.6%) had multidomain presentations, 45 (12.7%) had single-domain presentations, and 20 (5.6%) had no active disease features. Overall, the most common single-domain and multidomain presentations, respectively, were skin disease (12.7%) and PA + skin disease (11.7%). Multidomain presenters were more likely to have fibromyalgia, depression, anxiety, and prior biologic use than single-domain presenters. Multidomain presentations were associated with significantly worse patient and physician global assessments of disease activity, pain, and fatigue; Health Assessment Questionnaire-Disability Index and EuroQol 5-dimension scores; and work productivity at enrollment. In this US real-world cohort, most patients had multidomain disease presentations, which was associated with worse disease activity, QOL, and work productivity measures. This study highlights the heterogeneity of PsA and the importance of assessing all PsA domains for optimizing disease management.

Efficacy and Safety of CT-P13 in Inflammatory Bowel Disease after Switching from Originator Infliximab: Exploratory Analyses from the NOR-SWITCH Main and Extension Trials.

BackgroundThe NOR-SWITCH main and extension trials demonstrated that switching from originator to biosimilar infliximab (CT-P13) is efficacious and safe across six diseases. However, a subgroup analysis of Crohn’s disease (CD) in the main trial displayed a close to significant difference favouring originator infliximab, and more scientific data have therefore been requested. ObjectiveThe aim was to assess treatment efficacy, safety, and immunogenicity in an explorative subgroup analysis in CD and ulcerative colitis (UC) in the NOR-SWITCH trials.Patients and MethodsThe 52-week, randomised, non-inferiority, double-blind, multicentre, phase 4 NOR-SWITCH study was followed by a 26-week open extension trial where all patients received treatment with CT-P13. Treatment efficacy, safety, and immunogenicity in CD and UC were assessed throughout the 78-week study period.ResultsThe main and extension trials included 155 and 93 patients with CD and 93 and 80 patients with UC, respectively. Demographic and baseline characteristics were comparable in both treatment arms within patient groups. There were no differences in the main and extension trials regarding changes in activity indices, C-reactive protein, faecal calprotectin, patient’s and physician’s global assessment of disease activity and patient-reported outcome measures in CD and UC. Moreover, comparable results were also demonstrated for trough serum levels, presence of anti-drug antibodies, and reported adverse events.ConclusionEfficacy, safety, and immunogenicity of both the originator and biosimilar infliximab were comparable in CD and UC in the NOR-SWITCH main and extension trials. These explorative subgroup analyses confirm that there are no significant concerns related to switching from originator infliximab to CT-P13 in CD and UC.Trial RegistrationClinicalTrials.gov, number NCT02148640.Electronic supplementary materialThe online version of this article (10.1007/s40259-020-00438-7) contains supplementary material, which is available to authorized users.

Anti-granulocyte-macrophage colony-stimulating factor antibody otilimab in patients with hand osteoarthritis: a phase 2a randomised trial.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a key mediator of signs and symptoms in preclinical models of osteoarthritis. We explored the efficacy, safety, and pharmacokinetics of an anti-GM-CSF antibody, otilimab, in patients with hand osteoarthritis. This double-blind, randomised, placebo-controlled phase 2a study was done in 16 centres in the Netherlands, Germany, Poland, the UK, and the USA. Patients aged 18 years or older with inflammatory hand osteoarthritis, who had received at least one course of unsuccessful non-steroidal anti-inflammatory drugs, with two or more swollen and tender interphalangeal joints (on the same hand), signs of inflammation or synovitis identified with MRI in the affected hand, and a self-reported 24 h average hand pain intensity over the past 7 days of 5 or more on a 0-10 numerical rating scale were eligible for inclusion. Patients were randomly assigned (1:1) via interactive response technology (blocked randomisation; block size of four) to receive either subcutaneous otilimab 180 mg or placebo, administered weekly from week 0 to week 4, then every other week until week 10. Patients, investigators, and trial staff were masked to treatment; at least one administrator at each site was unmasked to prepare and administer treatment. The primary endpoint was change from baseline in 24 h average hand pain numeric rating scale averaged over 7 days before the visit at week 6. Secondary endpoints were: change from baseline in 24 h average and worst hand pain intensity at each visit; proportion of patients showing 30% and 50% reductions in 24 h average and worst hand pain intensity at each visit; change from baseline in Australian and Canadian Hand Osteoarthritis Index (AUSCAN) 3·1 numeric rating scale questionnaire components at each visit; change in number of swollen and tender hand joints at each visit; change from baseline in Patient and Physician Global Assessment of disease activity; serum concentration of otilimab; and safety parameters. Efficacy endpoints were assessed in the intention-to-treat population. The safety population included all patients who received at least one dose of study treatment. The study is registered with ClinicalTrials.gov, NCT02683785. Between March 17, 2016, and Nov 29, 2017, 44 patients were randomly assigned (22 in the placebo group and 22 in the otilimab group). At week 6, difference in change from baseline in 24 h average hand pain numeric rating scale between the otilimab and placebo groups was -0·36 (95% CI -1·31 to 0·58; p=0·44); at week 12, the difference was -0·89 (-2·06 to 0·28; p=0·13). Patients receiving otilimab showed greater improvement in AUSCAN components versus placebo at each visit. The change from baseline in the 24 h worst hand pain numeric rating scale in the otilimab group at week 6 showed a difference over placebo of -0·33 (95% CI -1·28 to 0·63; p=0·49); at week 12, this difference was -1·01 (95% CI -2·22 to 0·20; p=0·098). The proportion of patients achieving 30% or higher or 50% or higher reduction from baseline in the 24 h average and worst hand pain numeric rating scale scores was consistently greater (although non-significant) with otilimab versus placebo. Similarly, patients receiving otilimab showed greater improvement in AUSCAN pain, functional impairment, and stiffness scores versus placebo at each visit. No differences were observed between otilimab and placebo in the change from baseline in the number of swollen and tender joints across the study. The Patient Global Assessment was consistently lower than placebo at all visits; the Physician Global Assessment showed reductions across the study period, but the changes were similar in both treatment groups. Median otilimab serum concentrations increased during weekly dosing from 1730 ng/mL at week 1 to a maximum of 3670 ng/mL at week 4, but declined after transitioning to dosing every other week (weeks 6-10). In total, 84 adverse events were reported by 24 patients: 54 adverse events in 13 (59%) patients in the otilimab group and 30 adverse events in 11 (50%) patients in the placebo group. The most common adverse events were cough (reported in 4 [9%] patients; 2 in each group), and nasopharyngitis (in 3 [7%] patients; 1 in the placebo group and 2 in the otilimab group). Three serious adverse events occurred in this study (all in the otilimab group) and were deemed not related to the study medication. There were no deaths during the study. There was no significant difference between otilimab and placebo in the primary endpoint, although we noted a non-significant trend towards a reduction in pain and functional impairment with otilimab, which supports a potential role for GM-CSF in hand osteoarthritis-associated pain. There were no unexpected safety findings in this study, with no treatment-related serious adverse events reported. GlaxoSmithKline.

Age, Disease Symptoms, and Depression are Associated With Body Image Dissatisfaction in Newly Diagnosed Pediatric Inflammatory Bowel Disease.

Body image refers to the subjective, mental representation one makes regarding their physical appearance. Children and adolescents with inflammatory bowel disease (IBD) may be prone to experiencing negative self-evaluations regarding their body image given disease-related symptoms and treatment side-effects. In this study, we aimed to examine demographic, medical, and psychosocial variables related to body image dissatisfaction (BID) in pediatric patients diagnosed with IBD and to determine which variables are most predictive of higher dissatisfaction. A total of 52 youth newly diagnosed with IBD (Crohn's disease, ulcerative colitis, indeterminate colitis) ages 8 to 17 years completed questionnaires regarding their psychosocial functioning (ie, depression, anxiety, health-related quality of life, stress), disease symptoms, and BID. BID was assessed using the modified Adapted Satisfaction with Appearance questionnaire, yielding a total score and subscale scores assessing Perceived Social Impact and Subjective Dissatisfaction. Physician global assessment of disease activity and demographic and medical characteristics were abstracted from electronic chart review. Youth endorsed low overall BID concerns but noted the highest dissatisfaction with their abdomen, chest, and arms. Older child age, greater patient-reported disease symptoms, and worse depression symptoms were most strongly associated with overall body dissatisfaction when evaluated in a hierarchical regression model. Demographic, disease-related, and psychosocial factors are associated with BID in youth newly diagnosed with IBD. Given associations between BID and adverse health outcomes in healthy youth, these findings highlight a unique opportunity to improve screening and interventions for BID in patients with IBD.

Specific features of axial involvement in psoriatic arthritis: data from real clinical practice

Objective. To compare clinical features in psoriatic arthritis (PsA) patients with and without axial involvement. Subjects and methods. 385 PsA patients (172 males and 213 females) from National PsA Register were examined, their diagnosis verified according to CASPAR criteria. Patients’ median age was 45 [35; 54] years, median disease duration – 5,1 [0; 8] years. Pelvis X-ray and HLA-B27 levels in addition to physical examinations were obtained in all patients. Sacroiliitis (SI) was established based on radiographic findings (rSI) including bilateral changes corresponding to at least stage II, or unilateral – corresponding to at least stage III of Kellgren-Lawrence radiographic grading scale. Patients’ radiographs were evaluated by an independent radiologist. Disease activity was assessed using the DAS28 (Disease activity score 28), DAS (Disease activity in psoriatic arthritis) and BASDAI (Bath ankylosing spondylitis disease activity index) scales. 100 mm visual analog scale (VAS) was used for assessment of pain intensity (PI) and the Patient’s Global Assessment of Disease Activity (PtGA). Patients were distributed into two groups: Group 1 included rSI(+) patients, Group 2 – patients without radiologically confirmed SI – rSI (-). Results. Group 1 included 214 (55,6%) patients with axial involvement, 106 males and 108 females, Group 2 rSI (-) – 171 (44,4%) patients, 66 males and 105 females Proportion of men was significantly higher in RSi(+) group – 49,5% vs 38,6% in rSi(-) group (Odds Ratio, OR – 1,56, 95% CI 1,6-2,4; р = 0,0324). Patient’s median age was 45 [35; 54] and 46 [34; 56] years, respectively (p=0,911). Higher rates of HLA-В27 positivity were found in group rSI(+) patients, than in rSI(-), respectively in 62 out of 126 and in 26 out of 78 patients (OR 1,9, 95% CI 1,1-3,5). Patients from RSI(+) group had more severe erosive peripheral arthritis. Median tender joint counts (TJC) were 9 [14; 18] and 6 [3; 12] (р=0,02), while radiographic feet bone erosions were found in 58 (27,1%) and 29 (17%) patients, respectively (OR 1,8, 95% CI 1,1-3,0). Disease activity was higher in rSI(+) group. Median DAS28 score was 4,3 [3,3; 5,6] and 4,05 [3,03; 4,88] (р=0,02), DAPSA – 28,40 [15,65; 43,65] and 20,0 [12,45; 30,0], (р < 0,01), BASDAI – 1,6 [0; 5,1] and 0 [0; 4,5] (р < 0,01), C-reactive protein (CRP) – 0,9 [0,4; 2,2] mg/dl and 0,8 [0,3; 1,3] mg/dl, respectively (р=0,029). PtGA VAS values were 56,5 [42,3; 70,0] mm and 50,0 [30,0; 60,0] mm (р < 0,01); physicians global assessment (PGA) – 54,0 [40,0; 69,5] mm and 40,0 [25,5; 50,0] mm (р < 0,01); PI VAS values were 50,0 [40,0; 70,0] mm and 50,0 [20,5; 58,8] mm, respectively (р < 0,01). Higher rates of entheses involvement based on the Leeds Enthesitis Index (LEI) and dactylitis were documented in rSI(+) group. Median LEI score was 0 [0; 2] and 0 [0; 1] (p=0,02), while dactylitis was established in 71 (31,2%) and 32 (18,7%) patients, respectively (OR 2,2, 95% CI 1,3-3,5). More severe cutaneous involvement was also found in rSI(+) patients as compared to rSI (-). BSA (Body Surface Area) > 3% involvement was established in 94 (43,9%) and 57 (33,3%) patients, respectively (OR 1,7, 95% CI 1,03-2,4). Axial involvement was associated with more pronounced functional impairment. Median HAQ was 1,0 [0,6; 1,5] and 0 [0-2,2] (р=0,02). Conclusion. Axial involvement in PsA patients is associated with more severe articular damage, higher enthesitis and dactylitis rates, more severe psoriasis, which should be considered when planning treatment.

Efficacy and Safety of Baricitinib in Chinese Rheumatoid Arthritis Patients and the Subgroup Analyses: Results from Study RA-BALANCE.

IntroductionBaricitinib is an oral selective inhibitor of Janus kinase (JAK) 1 and JAK 2, which has demonstrated significant efficacy in patients with moderately to severely active rheumatoid arthritis (RA). This analysis aims to describe the efficacy and safety of baricitinib in Chinese RA patients with an inadequate response to methotrexate (MTX-IR), and to analyze the effects of baseline characteristics on the efficacy of baricitinib treatment.MethodsIn this 52-week, randomized, double-blind, placebo-controlled study, 231 Chinese patients with moderately to severely active RA who had MTX-IR were randomly assigned to placebo (n = 115) or baricitinib 4 mg once daily (n = 116). The primary endpoint was American College of Rheumatology 20% (ACR20) response at week 12. Other efficacy measures included ACR50, ACR70, Physician’s Global Assessment of Disease Activity, Patient’s Global Assessment of Disease Activity, patient’s assessment of pain, Disease Activity Score in 28 joints using high-sensitivity C-reactive protein, remission and low disease activity rates according to Simplified Disease Activity Index or Clinical Disease Activity Index, Health Assessment Questionnaire-Disability Index, and mean duration and severity of morning joint stiffness, worst tiredness and worst joint pain were analyzed. Additionally, subgroup analyses were performed across baseline characteristics.ResultsStatistically significant improvement in ACR20 response was achieved with baricitinib at week 12 (53.4 vs. 22.6%, p = 0.001) in Chinese patients, compared to placebo. Most of the secondary objectives were met with statistically significant improvements. Efficacy of baricitinib was irrespective of patient demographics and baseline characteristics. Safety events were similar between the baricitinib and placebo groups.ConclusionsThe efficacy of baricitinib 4 mg in Chinese patients with moderately to severely active RA and prior MTX-IR was clinically significant compared to placebo regardless of baseline characteristics. Baricitinib was well tolerated with an acceptable safety profile during the full study period.Trial RegistrationNCT02265705Electronic Supplementary MaterialThe online version of this article (10.1007/s40744-020-00231-6) contains supplementary material, which is available to authorized users.

Three-year clinical outcomes in patients with rheumatoid arthritis treated with certolizumab pegol: results from the observational ECLAIR study

To describe the long-term effectiveness and safety of certolizumab pegol in patients with moderate-to-severe rheumatoid arthritis (RA) in a real-world setting in France. ECLAIR was a 3-year longitudinal, prospective, observational, multicentre study. The primary objective was to describe the EULAR response after 1 year of certolizumab pegol treatment. Other endpoints included DAS28, clinical disease activity index, health assessment questionnaire disability index, fatigue assessment scale, patient's assessment of arthritis pain, patient and physician global assessments of disease activity, patient quality of life, and long-term safety. A total of 792 patients were enrolled, of whom 776 comprised the safety set, and 733 the full analysis set. In the full analysis set, 559, 469 and 430 patients had a 12-, 24- and 36-month visit, respectively. This included 378, 296 and 246 patients still receiving certolizumab pegol at these visits. The percentage of EULAR responders was 75.3% (305/405 patients with an available EULAR response) at 12, 76.5% (261/341) at 24, and 79.6% (226/284) at 36 months. Among those still receiving certolizumab pegol, the percentage of EULAR responders was 81.7% (237/290) at 12, 81.1% (185/228) at 24, and 87.3% (158/181) at 36 months. Sustained improvements were observed in other effectiveness outcomes. Overall, 45.1% (350/776) of patients experienced 776 adverse drug reactions. No new safety signals were identified. This is the first prospective, observational study of an anti-TNF treatment in France. The results confirm the effectiveness and safety profile of certolizumab pegol treatment in patients with RA in a real-world setting.

Outcome Measures in Large Vessel Vasculitis: Relationship Between Patient-, Physician-, Imaging-, and Laboratory-Based Assessments.

To assess the relationship between measures of disease assessment in patients with large vessel vasculitis. Patients with giant cell arteritis (GCA) or Takayasu arteritis (TAK) were recruited into a prospective, observational cohort. Assessments within the following outcomes were independently recorded: 1) patient-reported outcomes (Multidimensional Fatigue Inventory, patient global assessment of disease activity [PtGA], Short Form 36 health survey [SF-36], Brief Illness Perception Questionnaire), 2) physician global assessment of disease activity (PhGA), 3) laboratory outcomes (C-reactive protein [CRP] level, erythrocyte sedimentation rate [ESR]), and 4) imaging outcomes (PETVAS, a qualitative score of vascular 18 F-fluorodeoxyglucose-positron emission tomography activity). Analyses were performed on 112 patients (GCA = 56, TAK = 56), over 296 visits, with a median follow-up of 6 months. Correlation network analysis revealed assessment measures clustered independently by type of outcome. PhGA was centrally linked to all other outcome types, but correlations were modest (ρ = 0.12-0.32; P < 0.05). PETVAS, CRP level, and PtGA were independently associated with clinically active disease. All 4 patient-reported outcomes strongly correlated with each other (ρ = 0.35-0.60; P < 0.0001). Patient-reported outcomes were not correlated with PETVAS, and only PtGA correlated with CRP level (ρ = 0.16; P < 0.01). Patients whose clinical assessment changed from active disease to remission (n = 29) had a corresponding significant decrease in ESR, CRP level, and PETVAS at the remission visit. Patients whose clinical assessment changed from remission to active disease (n = 11) had a corresponding significant increase in CRP level and PtGA at the active visit. Measures of disease assessment in large vessel vasculitis consist of independent, yet complementary, outcomes, supporting the need to develop composite outcome measures or a standard set of measures covering multiple types of outcomes.

Impact of Comorbidities on Disease Activity, Patient Global Assessment, and Function in Psoriatic Arthritis: A Cross-Sectional Study.

IntroductionThe aim of this study was to evaluate the impact of comorbidities on disease activity, patient’s impact of the disease, patient global assessment, and function in psoriatic arthritis (PsA).MethodsConsecutive PsA patients were enrolled in this cross-sectional study. During the visit, the patients underwent a complete physical examination and clinical/laboratory data were collected, including type and number of comorbidities, recorded as simple comorbidity count (SCC).Disease activity was assessed using the Disease Activity Score for Psoriatic Arthritis (DAPSA) and the Minimal Disease Activity (MDA) was also evaluated. The Psoriatic Arthritis Impact of Disease (PsAID), the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Patient Global Assessment of disease activity (PtGA) were also collected.ResultsA total of 144 patients were enrolled. At least one comorbidity was registered in 104 (72.2%) patients. The SCC was associated with DAPSA (β = 1.48, p = 0.013), PsAID (β = 0.41, p < 0.01), HAQ-DI (β = 0.11, p < 0.01) and PtGA (β = 0.50, p < 0.01). The comorbidities that showed an impact on outcome measures were anxiety and fibromyalgia (FM). Anxiety showed an impact on DAPSA (β = 14.46, p < 0.001), PsAID (β = 1.98, p = 0.039) and HAQ-DI (β = 0.54, p = 0.036). FM showed an impact on DAPSA (β = 6.46, p = 0.025), PsAID (β = 2.88, p < 0.001), HAQ-DI (β = 0.70, p < 0.001), PtGA (β = 2.00, p = 0.014), and MDA (β = − 2.79, p = 0.01). The median PtGA value was different among patients with different numbers of comorbidities.ConclusionsThis study showed that comorbidities, either as a simple comorbidity count number or as single comorbidity, might have an impact on the main domains affecting PsA patients in real clinical practice.

Time to remission in swollen joints is far faster than patient reported outcomes in rheumatoid arthritis: results from the Ontario Best Practices Research Initiative (OBRI).

RA patients are often not in remission due to patient global assessment of disease activity (PtGA) included in disease activity indices. The aim was to assess the lag of patient-reported outcomes (PROs) after remission measured by clinical disease activity index (CDAI) or swollen joint count (SJC28). RA patients enrolled in the Ontario Best Practices Research Initiative registry not in low disease state at baseline with at ≥6 months of follow-up, were included. Low disease state was defined as CDAI ≤ 10, SJC28 ≤ 2, PtGA ≤ 2cm, pain score ≤ 2cm, or fatigue ≤ 2cm. Remission included CDAI ≤ 2.8, SJC28 ≤ 1, PtGA ≤ 1cm, pain score ≤ 1cm, or fatigue ≤ 1cm. Time to first low disease state/remission based on each definition was calculated overall and stratified by early vs established RA. A total of 986 patients were included (age 57.4 (12.9), disease duration 8.3 (9.9) years, 80% women). The median (95% CI) time in months to CDAI ≤ 10 was 12.4 (11.4, 13.6), SJC28 ≤ 2 was 9 (8.2, 10), PtGA ≤ 2cm was 18.9 (16.1, 22), pain ≤ 2cm was 24.5 (19.4, 30.5), and fatigue ≤ 2cm was 30.4 (24.8, 31.7). For remission, the median (95% CI) time in months to CDAI ≤ 2.8 was 46.5 (42, 54.1), SJC28 ≤ 1 was 12.5 (11.4, 13.4), PtGA ≤ 1cm was 39.6 (34.6, 44.8), pain ≤ 1cm was 54.7 (43.6, 57.5) and fatigue ≤ 1cm was 42.6 (36.8, 48). Time to achieving low disease state and remission was generally significantly shorter in early RA compared with established RA with the exception of fatigue. Time to achieving low disease state or remission based on PROs was considerably longer compared with swollen joint count. Treating to a composite target in RA could lead to inappropriate changes in DMARDs.

Interferon blockade in systemic lupus erythematosus: Light at the end of the tunnel for novel therapies for lupus?

Interferon blockade in systemic lupus erythematosus: Light at the end of the tunnel for novel therapies for lupus?

Performance of the 2017 EUSTAR activity index in an scleroderma cohort

Assessment of disease activity in systemic sclerosis (SSc) is limited by the absence of a fully validated, multisystem measure of disease activity. The European Scleroderma Trials and Research Group (EUSTAR) SSc activity index (EScSG-AI) was recently revised, and a validation study within the EUSTAR cohort was performed. In this study, we evaluated the performance of the revised EScSG-AI in an external Australian cohort. The association between the EScSG-AI and the physician global assessment of disease activity (PhGA), both collected prospectively at each annual visit over up to 12years follow-up, was evaluated using Pearson's correlation coefficient and Cohen's kappa coefficient. Generalized linear modelling and time-dependent Cox regression analysis were performed to determine the association of disease activity measured by the EScSG-AI and the summed Medsger Severity Scale (MSS) and death, respectively. There was a moderate correlation between EScSG-AI and PhGA scores (r 0.42, p < 0.001) and moderate association between rising EScSG-AI and summed MSS (r 0.60, p < 0.001). High disease activity, measured by the EScSG-AI at any time during follow-up, was associated with a hazard ratio of 2.07 (95% CI 1.51-2.79) for mortality. The EScSG-AI has a moderate correlation with physician-assessed SSc disease activity. This suggests that the criterion and construct validity of the EScSG-AI are yet to be demonstrated in an external cohort of SSc patients. Key Points •There remains no gold standard measure of SSc disease activity. •The revised 2017 EUSTAR SSc disease activity index shows moderate correlation with physician-rated global disease activity. •Significant work remains to develop a validated multisystem measure of disease activity in SSc.

Translation, Cross-cultural Adaptation and Validation of Ankylosing Spondylitis Disease Activity Score

Ankylosing Spondylitis Disease Activity Score (ASDAS) is a very important tool for measuring disease activity in patients with axial spondyloarthritis (axSpA). This study was aimed to develop a culturally adapted, valid and reliable Bengali version of questionnaire for the ASDAS. The original English ASDAS was translated into Bangla and adapted in the local socio-cultural context, following standard international recommendations. Content validity of the adapted Bangla version was assessed by the item-level &amp; scale level content validity indices (I-CVI &amp; S-CVI). A total 120 patients with axSpA were assessed in the study. For construct validity, correlation between ASDAS with BASDAI, ESR, CRP, Maastricht enthesitis score, physician's global assessment and BASMI was assessed by Spearman's rank correlation coefficient. Internal consistency and test-retest reliability were assessed using Cronbach's alpha coefficient and intraclass correlation coefficient respectively. I-CVI for each item was 1 and S-CVI was 1. ASDAS-ESR and ASDAS-CRP showed strong correlation (Spearman's correlation coefficient &gt;0.5) with BASDAI, ESR, MASES and physician global assessment of disease activity. The scale demonstrated excellent internal consistency (Crohnbach's alpha=0.703) and test-retest reliability (ICC=0.98). The adapted Bangla version of the ASDAS demonstrated acceptable psychometric properties (validity &amp; reliability) in Bangladeshi patients with axSpA. Faridpur Med. Coll. J. Jul 2019;14(2): 62-66

Comparative results of the implementation in daily practice of an evaluation checklist for patients with axial spondyloarthritis and psoriatic arthritis

ObjectiveTo analyse and compare changes in the collection of clinical variables after the implementation in daily practice of an evaluation checklist for patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). MethodsAn observational study was performed based on medical records review. The number and type of variables of the evaluation checklist in the medical records were collected. The first review was made before the implementation of the checklist, and the second one 6 months after the implementation (in different patients). A descriptive and bivariate analysis was carried out. ResultsSix hospitals and 11 rheumatologists participated. A total of 83 and 68 medical records were reviewed before and after the implementation of the checklist. After the implementation, in the axSpA patients, a significant increase was recorded in alcohol consumption, diarrhoea or IBD and urethritis, diabetes mellitus, hyperlipidaemia, depression, obesity or gout/hyperuricaemia, weight, height, blood pressure, patient and physician global assessments of disease activity, BASDAI and DAS28. And, in the PsA patients, alcohol consumption, hypertension, diabetes mellitus, hyperlipidaemia, disease, gout/hyperuricaemia, thoracic expansion, cervical rotation, weight, height, blood pressure, patient and physician global assessments of disease, ASDAS, BASDAI, and BASFI were recorded. In general, there was a trend towards greater recording in axSpA compared with PsA. ConclusionsThe implementation of a specific checklist in daily practice improves the evaluation of patients with axSpA and PsA. More efforts are necessary to continue improving the evaluation of patients with axSpA, but especially of those with PsA.

THU0111 PHYSICIAN’S GLOBAL ASSESSMENT OF DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS: WHAT DO WE REALLY MEAN?

Background:Physician’s global assessment of disease activity (PhGA) is included in some scores of disease activity and, demonstrably, plays a major role upon treatment decisions in rheumatoid arthritis (RA) [1, 2, 3]. Therefore, understanding the reasons underlying the physician´s assessment is crucial.Objectives:To understand the reasons underlying the physician´s assessment.Methods:Cross-sectional study, including consecutive RA patients followed in a Tertiary Rheumatology Department. Socio-demographic (age and gender) and clinical data were collected through a standardized protocol, including 28 tender (TJ28) and swollen (SJC28) joints count, C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), Disease activity Score (DAS28-4v-CRP and DAS28-4v-ESR), PhGA and Patient Global Assessment of disease Activity (PGA) through a Visual Analogic Scale (VAS) 0-100mm, Health Assessment Questionnaire (HAQ), European Quality of Life-5 Dimensions (EQ-5D) and Hospital Anxiety and Depression Scale (HADS). Correlation between PhGA and other continuous variables was evaluated through Pearson´s Correlation Coefficient and variables with p&lt;0.05 in univariate analysis were included in multivariable linear regression (stepwise model).Results:392 RA patients (80.6% female, 65.3±12.6 years) were included. PhGA was weakly correlated with CRP (r=0.23), TJC28 (r=0.35), PGA (r=0.26), HAQ (r=0.31) and EQ5D (r=-0.21). Moderate correlations were observed with SJC28 (r=0.45) and DAS-4V-CRP (r=0.48). In multivariable analysis, SJC28 (β=4.14, 95%CI:3.16-5.12), CRP (β=0.22; 95%CI: 0.02-0.03), HAQ (β=4.46, 95%CI:1.50-7.42) and PGA (β=0.08; 95%CI:0.00-0.16) remained as independent correlates of PhGA (R2=0.27, p&lt;0,05).Conclusion:In this study, PhGA was associated with SJC28, CRP, HAQ and PGA, suggesting that physicians adopt a comprehensive reading of the disease into account. However, a large proportion of the variance of PhGA remains unexplained. Given its driving role in treatment decisions, the need to standardize and better understand PhGA seems to deserve a closer attention.

THU0116 IS THE ROLE OF MEDICAL CONSULTATION IN RHEUMATOID ARTHRITIS A TIMELY TOPIC?

Background: Despite the treat-to-target recommendations and the efforts in dissecting factors that contribute to achieving disease control, the goal of remission in rheumatoid arthritis (RA) is accomplished in less than half of patients. Disease activity is assessed using composite indexes which are reliant on patient-reported outcomes, mainly the patient global assessment of disease activity (PGA). The debate on variables that can influence PGA is still open, and different internal and external factors had been taken into account: the origin of pain symptoms, psychosocial and lifestyle factors. Objectives: To canvass the opinion of RA Italian patients concerning patient-perceived topics that matter most for future research. Methods: A cross-sectional no-profit on-line anonymous survey was devised to evaluate opinions of the rheumatic diseases patients. In this sub-study we focused only on the data about RA patients. Patients were asked to rate the following topics: food/nutrition, air pollution, smoking, type of work, social participation, physical activity, emotional well-being/stress, alternative medicine, patient-physician relationship. Moreover, patients were inquired about why the topic was considered important (disease prevention, stop disease progression, control symptoms, cure the disease). The survey was disseminated between June and October 2019. Descriptive statistics were used to summarize the patient demographic, clinical data and survey results. Results: 94% (82/87) of RA patients (81 female, median age 50 yrs) rated the patient-physician relationship as the main topic for future research (figure below). Likewise, intriguing results came from the reasons of previous patient rating: the patient-physician relationship was considered important for a better control of RA symptoms (48.8%), to cure the disease (30.5%), to stop disease progression (19.5%), and to prevent the disease (1.2%). These results were similar in all age groups. Conclusion: These results highlight that the importance of medical consultation to patients and its impact on disease control should not be under-estimated. Administrative duties, time and economic constraints undermine the patient-physician relationship that is central to clinical care. The limited time spent for medical consultation is directly related to patient dissatisfaction, which in turn, may influence the patient’s perception about the absence of disease activity and could be one of motives behind the worse evaluation of PGA. Acknowledgments: We wish to thank the Lombard Association of Rheumatic Diseases (ALOMAR), Maria Vittoria Ausilio and Patrizia Angiolillo from the IT service of the University of Milan. Disclosure of Interests: Francesca Ingegnoli: None declared, Tania Ubiali: None declared, Tommaso Schioppo: None declared, Silvia Ostuzzi: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB

THU0137 ASSESSING THE MULTIMORBID PROFILE (CIRS) IN RHEUMATOID ARTHRITIS. FIRST RESULTS.

Background:Objectives:To assess the presence and nature of multimorbidity in patients with rheumatoid arthritis (RA) and the impact of multimorbidity on disease activity.Methods:The investigation enrolled 117 patients (mean age, 54.8±14.8 years) with RA according to the 2010 ACR/EULAR criteria, who had been examined and treated at the V.A. Nasonova Research Institute of Rheumatology in 2018–2019. The median disease duration was 5.0 [1.5; 9.5] years; the mean DAS28 score was 5.0±1.3. Documentation and anamnesis data were analyzed with emphasis on associated diseases. The Cumulative Illness Rating Scale (CIRS) was used to assess the profile of multimorbidity.Results:The patients with RA had a high index of the spectrum of multimorbidity; concomitant diseases were detected in 96 (82%) cases.The median number of diseases in one patient was 2 [1; 4], the mean total CIRS score was 6.7±3.3; the median value was 2.5 [1; 6]. The number of concomitant diseases diagnosed before using the CIRS was significantly lower (by 48%; p&lt;0.01) than was found in the investigation conducted.Chronic kidney disease that occurred in almost half (42.5%) of cases was most commonly undiagnosed in the cohort under study; on average, every three patients were not found to have signs of metabolic syndrome (hyperglycemia in 29%, hypercholesterolemia in 20%, obesity in 13.5%), chronic hypoxia (new-onset anemia verified in 24% of cases). In 12% of cases lung damages were not found before using the CIRS. There was a correlation of the quantitative equivalent of multimorbidity with the clinical and laboratory measures of RA activity, including the number of painful joints (r = 0.39; p&lt;0.001), overall patient assessment (r=0.37; p=0.03), physician’s global assessment of disease activity (r = 0.37; p &lt; 0.01), DAS28 (r = 0.42; p&lt;0.001), CDAI (r=0.37; p&lt;0.001), SDAI (r=0.34; p&lt; 0.001), HAQ (r=0.34; p&lt;0.001). The total CIRS score did not differ in patients with early- and advanced- or end-stage RA: 6.6±3.5 and 6.7±3.3, respectively (p=0.9).Conclusion:A systematic screening of multimorbidity should be carried out in all patients with RA. It is advisable to use the CIRS to estimate the prevalence of multimorbidity, its consequences and the risk factors for the development of multimorbidity in the long term.Disclosure of Interests:None declared

OP0050 ADALIMUMAB INTRODUCTION VERSUS METHOTREXATE DOSE ESCALATION IN PATIENTS WITH INADEQUATELY CONTROLLED PSORIATIC ARTHRITIS: RESULTS FROM RANDOMIZED PHASE 4 CONTROL STUDY

Background:Methotrexate (MTX) is often used as first-line therapy for patients (pts) with psoriatic arthritis (PsA) despite limited efficacy and data on appropriate dosage. Minimal Disease Activity (MDA) is suggested as an optimal treat-to-target outcome. Biologic disease-modifying antirheumatic drugs (bDMARDs) have demonstrated improved outcomes (including MDA rates) over MTX. However, more data are needed to define the optimal timing of bDMARD initiation and characterize efficacy of MTX dose escalation, to achieve optimal outcomes.Objectives:To compare achievement of MDA between adding adalimumab (ADA) vs escalating MTX dose in PsA pts with inadequate disease control after initial MTX therapy.Methods:The open-label, 2-part CONTROL study enrolled bDMARD-naive adult pts with active PsA (not in MDA at screening and ≥3 tender and ≥3 swollen joints) despite MTX 15 mg every wk (ew) for ≥4 wks. Pts were randomized to ADA 40 mg every other wk + MTX 15 mg (ADA+MTX) or escalated MTX to 20–25 mg ew or highest tolerable dose during 16-wk part 1 (Fig 1). The primary endpoint was achievement of MDA, defined as fulfilling ≥5 of the 7 criteria: tender joint count 68 (TJC68) ≤1, swollen joint count 66 (SJC66) ≤1, Psoriasis Area Severity Index (PASI) ≤1 or body surface area (BSA) ≤3%, pt’s pain (visual analogue scale [VAS] 0–100) ≤15, Pt’s Global Assessment of disease activity (PtGA) VAS ≤20, Health Assessment Questionnaire Disability Index (HAQ-DI) ≤0.5 and tender entheseal points (0–8) ≤1. Key secondary efficacy endpoints were achievement of ACR20 and PASI75 and change from baseline in HAQ-DI and Leeds Enthesitis Index (LEI) at wk 16.Results:Overall, 246 pts were randomized; 245 received treatment (ADA+MTX, n=123; escalated MTX, n=122); 117 (95%) pts and 110 (90%) pts, respectively, completed part 1. Baseline characteristics were similar between groups (Table). During part 1, the average dose of MTX was 21.8 mg/wk (55% on oral MTX) in the escalated MTX group. Significantly higher proportion of pts in ADA+MTX (42%) vs escalated MTX (13%) group achieved MDA at wk 16 (non-responder imputation [NRI]; difference [95% CI] 28% [18%–39%];P&lt;0.001;Fig 2). Observed case analysis confirmed the NRI analysis. Lower MDA rates at wk 16 were observed in the escalated MTX arm regardless of prior MTX duration (Fig 2). Significant improvements in key secondary endpoints were also observed with ADA+MTX vs escalated MTX (allP&lt;0.05;Fig 2). In part 1, the proportion of patients with adverse events was similar between groups (ADA+MTX, 62% vs escalated MTX, 57%); no opportunistic infections, tuberculosis, malignancies, or deaths were reported during part 1.Conclusion:A significantly higher proportion of pts achieved MDA at wk 16 after introducing ADA compared with escalating MTX dose; higher rates were observed regardless of prior MTX duration. Significantly higher responses in musculoskeletal, skin, and quality of life measures were observed with ADA+MTX vs escalated MTX. No new safety signals with ADA were identified in this pt population.Table 1.Baseline DemographicsCharacteristics, mean (SD)ADA+MTXn=123Escalated MTXn=122Female, n (%)64 (52.0)59 (48.4)Age, y51.4 (12.2)48.8 (12.7)BSA &gt;3%, n (%)74 (60.2)78 (63.9)Pt pain63.7 (19.5)62.3 (20.9)PtGA65.0 (19.9)62.9 (20.9)HAQ-DI1.2 (0.6)1.2 (0.7)LEI + plantar count3.5 (2.1)3.5 (2.1)Disclosure of Interests:Laura C Coates: None declared, William Tillett Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc, UCB, Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc, UCB, Maria Antonietta D’Agostino Consultant of: AbbVie, BMS, Novartis, and Roche, Speakers bureau: AbbVie, BMS, Novartis, and Roche, Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Frank Behrens Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Lilly and Roche, Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai, Philip G Conaghan Consultant of: AbbVie, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, GSK, Novartis, Pfizer, Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Erin McDearmon-Blondell Shareholder of: AbbVie, Employee of: AbbVie, Xianwei Bu Shareholder of: AbbVie, Employee of: AbbVie, Liang Chen Shareholder of: AbbVie, Employee of: AbbVie, Mudra Kapoor Shareholder of: AbbVie, Employee of: AbbVie, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau